Chlamydia trachomatis remains a significant cause of sexually transmitted disease in the United States and Europe. The major concern with chlamydial genital infections is the development of salpingitis which may result in tubal obstruction and infertility. While the pathogenesis of salpingitis is still not clear, it is basically agreed that the primary site of infection is the endocervix with subsequent canalicular spread to the endometrium and fallopian tubes. Current evidence indicates that ascending infection develops in a significant number of individuals but the reasons why only a certain proportion of women develop clinical salpingitis is not known. Furthermore, the mechanism of salpingitis is undefined, although evidence suggests that multiple occurrences increases the incidence of tubal obstruction. In this study, guinea pigs infected in the genital tract with the chlamydia gent of guinea pig inclusion conjunctivitis (GPIC) will be used as a model system. Intravaginal inoculation of chlaymydiae in the guinea pig results routinely in ascending infection with the development of salpingitis. This phenomenon will be characterized with regard to the dose of GPIC required, the time frame of development of the disease, the cellular makeup of the pathological changes, and the relationship to the stage of the estrous cycle. The effect of multiple infections and the possible immunopathological etiology of salpingitis will be studied. Since prevention of reinfection by immunization with inactivated antigens has not proved wholly successful, the strategy of immunization with the objective of preventing ascending infection and tubal disease will be explored. Guinea pigs will be immunized with inactivated organisms and challenged intravaginally. The effectiveness will be assessed by examination of the fallopian tubes at various times for pathology and chlamydiae. The duration of any protective effect will also be determined. In addition, the possibility of immunopathological sequellae will be evaluated. Finally, specific chlamydial outer membrane components including the major outer membrane component, a 61- kDA protein, and lipopolysaccharide will be isolated and used as immunogens to determine which may possess a protective epitope(s). Further screening studies will be injected into guinea pigs and their protective ability assessed.